Fibrinogen Nový Jičín and Praha II: Cases of hereditary Aα 16 Arg → Cys and Aα 16 Arg → His dysfibrinogenemia

Abstract

Introduction Various dysfibrinogenemias have been described worldwide. This paper describes two new cases of dysfibrinogenemia identified in the Czech Republic. Materials and methods The proposita of fibrinogen Nový Jičín, a 12-year-old girl, presented with hemorrhagic complications, low Clauss fibrinogen level (0.3 g/l) and prolonged both thrombin (70.8 s) and reptilase (> 180 s) time. Her mother and sister both presented with normal coagulation tests, normal fibrinogen level and reported no history of bleeding. The carriers of the fibrinogen Praha II were a 31-year-old man and his 11-year-old daughter. They both presented with low fibrinogen Clauss level (0.88 g/l) and prolonged thrombin and reptilase time. To identify the genetic mutation responsible for these dysfibrinogens, genomic DNA extracted from the blood was analyzed. The presence of the mutant chains in the circulation was determined by MALDI-TOF mass spectroscopy. Scanning electron micrographs of the patients' fibrin clots were obtained. Results The kinetics of fibrinopeptide release and fibrin polymerization were impaired for both fibrinogen Nový Jičín and Praha II. DNA sequencing showed heterogeneous fibrinogen Aα R16C mutation in the fibrinogen Nový Jičín case and heterogeneous fibrinogen Aα R16H in the fibrinogen Praha II case. The mutant chains were found to be expressed to the circulation by MALDI-TOF mass spectroscopy. Scanning electron micrographs of the patient's fibrin clot were found to be abnormal. Conclusions The case of dysfibrinogenemia Aα R16C-fibrinogen Nový Jičín and the case of dysfibrinogenemia Aα R16H were found by routine coagulation testing and were genetically identified.